Many solid tumors are presently known to involve the infiltration of autologous lymphocytes. These autologous lymphocytes, known as tumor-infiltrating lymphocytes (TIL), have been shown to recognize specific antigens expressed by cells of the solid tumor. Expression of such tumor-associated antigens (TAAs) in combination with appropriate accessory signals leads to a specific cytolytic (cytotoxic) reactivity of the TILs toward the solid tumors. In addition, antibodies that can recognize similar and unique antigens have also been shown to bind selectively to and facilitate killing of tumor cells.
Several tumor antigens have been identified in association with a variety of tumors (Boon, et al. (1994). Ann Rev Immunol, 12:337; Kawakami, et al. (1994). Proc Natl Acad Sci USA, 91:3515; and Bakker, et al. (1994). J Exp Med, 179:1005). In addition to the identification of TAAs, immunodominant epitopes recognized by TILs have also been described for widely-expressed lineage-specific antigens, for example, the HLA-A2-restricted Melan-A/MART-1 in melanomas (Sensi, et al., (1995). Proc Natl Acad Sci USA, 92:5674; and Kawakami, et al., (1994). J Exp Med, 180:347).
Although there is mounting evidence that it is possible to induce cell mediated immunity against autologous melanomas, clinical immunotherapy strategies (Kradin, et al. Cancer Immunol. Immunother. (1987). 24:76); Kradin, et al. Lancet, (1989). 1:577; Rosenberg et al., (1987). N. Eng. J. Med., (1988). 25:1676; Dillman, et al. (1991). Cancer, 68:1; Gattoni, et al., (1966). Semin. Oncol, 23:754; and Kan-Mitchell, et al. (1993). Cancer Immunol. Immunother., 37:15), have failed to achieve routine efficacy. This failure has been due, at least in part, to the ability of tumors to evade immune destruction (Becker, et al., (1993). Int. Immunol., 5:1501; Jager, et al. (1997). Int. J. Cancer, 71:142; Macurer, et al., (1996). J. Clin. Invest., 98:1633; and Marincola, et al., (1996). J. Immunother. Emphasis Tumor Immunol., 9:192).